IN FAVOR OF AN ONCOFETAL CONCEPT OF BRONCHOGENIC-CARCINOMA DEVELOPMENT

Our recent studies in a heterotopic model of non-small cell lung cance r in dogs (subcutaneous bronchial autografts treated with 3-methylchol anthrene) have provided evidence that alveolar type II cells may newly arise during initial phases of bronchial carcino-genesis. In the ligh t of these novel findings, which are in agreement with our observation s in human non-small cell lung cancer, and in view of present insights into embryonic lung differentiation, we discuss evidence that favours a new, oncofoetal concept of bronchogenic carcinoma development. Acco rding to this concept, the primary cells of origin for these tumors ar e undifferentiated primordial-like cells that derive from bronchial ep ithelial cells present in major bronchi or their divisions by retrodif ferentiation. Such primordial-like cells of origin undergo novel diffe rentiation into the potential (alveolar, bronchial or primordial) tumo r stem cells, which occupy the dividing cellular layers of the (pre)ne oplastic lesions and constitute the actively dividing and invading par t of the neoplasm. Examples of tumors that may originate from alveolar tumor stem cells are carcinomas of the bronchioloalveolar, papillary, acinar, and adenoid-cystic types. Squamous cell carcinomas could poss ibly belong to this group as well, but much more evidence is required to reach conclusions regarding this type of cancer. We suggest that ep ithelial retrodifferentiation followed by novel differentiation (oncof oetal mechanism) is fundamental in bronchial carcinogenesis.